Alzheimer's Disease (AD), the major cause of dementia in the elderly, is likely to be caused by a combination of aging, genetic and environmental factors. While the evidence that AD is at least in part genetically determined, little is known with any certainty about non-genetic risk factors. A powerful method of determining risk factors for AD would be to identify populations from the same ethnic group at different levels of development and in different environments with varying rates of illness. The Indianapolis-Ibadan Dementia project has now established two population-based cohorts of community-dwelling elderly African Americans (N=2212) and Africans (N=2494), carefully evaluated with identical methodology. So far two major findings have resulted from this study. The age-adjusted prevalence of AD is significantly lower in Africans than in African Americans. In pilot studies, the allele of apolipoprotein E (APOE) had a strong association with AD in African Americans equal to that in Caucasian populations. In Africans the APOEepilon4 allele is a significant risk factor for AD in incidence cases in African Americans but not in Africans. The secondary aims of the studies are: 3) to identify risk factors for incidence cases of AD from data collected prior to the onset of disease; 4) to describe the natural history of cognitive and social functioning over a six year period in the two community dwelling cohorts and to identify factors which may predict decline in cognitive and social functioning; and 5) to store blood, plasma and DNA samples for future genetic and biological studies. In order to accomplish these goals, we are proposing a five-year longitudinal study with two incidence phases in years two and four. Subjects who are diagnosed with dementia will have follow-up clinical assessments in years one, three and five. We are also planning to determine the APOE genotypes of all subjects who consent to this procedure in the two samples and to continue to collect other risk factor data.